Role of TP53 P72R polymorphism in human papillomavirus associated premalignant laryngeal neoplasm.
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Adolescent↗
Biomedical subjects
A Vaheri
Publications and source records attributed to A Vaheri.
Mucin MUC1 is seen in cell surface protrusions together with ezrin in immunoelectron tomography and is concentrated at tips of filopodial protrusions in MCF-7 breast carcinoma cells.
MUC1, a transmembrane member of the mucin family, is believed to have anti-adhesive properties because of its highly sialylated, extended, and rigid rod-like conformation. The ERM proteins (ezrin, radixin, and moesin) function as membrane-cytoskeletal linkers. MUC1 and ezrin are enriched in microvilli in MCF-7az breast carcinoma cells. Similar localization was also found in peripheral membrane areas and in filopodium-like protrusions. Whereas ezrin was consistently detected in the cell-cell contact region, MUC1 was less frequently found there. MUC1 was distinctly expressed in long filopodial protrusions and was highly concentrated at their tips, which also contained ezrin, whereas F-actin was found along the stalk. This localization of MUC1 suggests a role for MUC1 in transient cell structures of migrating cells and transient cell adhesion. No direct association has yet been found between MUC1 and ezrin. However, both MUC1 and ezrin had a similar overall distribution pattern in microvilli and filopodium-like protrusions in immunoelectron tomography. In addition, MUC1 and ezrin showed spatial association, because several 10-nm gold particles used to decorate ezrin were seen in the vicinity close to the clusters of 5-nm gold particles decorating MUC1. Therefore, MUC1 appears to be associated with ezrin, but the nature of this association requires further study.
Cytoskeletal Proteins↗
Elimination of hydrocortisone from the medium enables tissue plasminogen activator gene expression by normal and immortalized nonmalignant human epithelial cells.
Human cervical epithelial cells transfected and immortalized with human papillomavirus type 16 DNA (HCE16/3) can be, like many other epithelial cells, normally grown in medium supplemented with epidermal growth factor, cholera toxin, hydrocortisone, insulin, transferrin, thyroid hormone and serum. We found that hydrocortisone diminished tissue plasminogen activator (tPA) production to an undetectable level. The removal of hydrocortisone increased urokinase plasminogen activator (uPA) activity within 24-48 h and tPA activity within 48-72 h, and converted the cells to a more elongated and fibroblastic phenotype. Upregulation of uPA mRNA was seen as early as at 3 h and of tPA mRNA within 48-72 h. Higher molecular weight forms (97-110 kDa) of plasminogen activators were seen in zymograms, apparently complexed with PAI-1, starting at 6 h both in the presence and absence of hydrocortisone. Immunoprecipitation with a PAI-1 monoclonal antibody confirmed that both uPA and tPA were complexed. We also studied normal diploid human bronchial epithelial cells (NHBE) and NHBE cells transformed with an adeno-12/SV40 hybrid virus (BEAS-2B). In both types of nonmalignant epithelial cells, the removal of hydrocortisone increased uPA activity. The omission of hydrocortisone increased tPA levels significantly in BEAS-2B cell cultures, and in NHBE cell cultures tPA became detectable at 72 h. No PA complexes were seen in these two cell types. We conclude that normal and immortalized nonmalignant epithelial cells produce tPA, but only if hydrocortisone is omitted in the growth medium.
Blotting, Northern↗
Ezrin as a prognostic indicator and its relationship to tumor characteristics in uveal malignant melanoma.
PURPOSE: Immunohistochemistry was used to investigate whether uveal malignant melanoma expresses ezrin, a protein involved in cell migration and cell recognition by acting as a linker between the plasma membrane and actin cytoskeleton. Also investigated was whether ezrin immunoreactivity correlates with survival prognosis. METHODS: A monoclonal antibody, 3C12, that reacts with the carboxyl-terminal part of ezrin was used in retrospective analysis of a population-based cohort of 167 consecutive choroidal and ciliary body melanomas in eyes enucleated from 1972 through 1981, with a median follow-up of 22 years. RESULTS: Ezrin immunoreactivity in tumor cells was graded negative in 47 (36%) melanomas, positive in 74 (57%), and strongly positive in 9 (7%). The immunoreactivity tended to be homogenous throughout the tumor, with focal concentrations along the cell surface. Positive reaction was significantly associated with high microvascular density (P < 0.001) and presence of macrophages (P < 0.001), but not with tumor size, cell type, or microvascular loops and networks. The 10-year melanoma-specific survival was significantly associated with ezrin immunoreactivity (P = 0.018). After adjustment by Cox regression for tumor size, cell type, microvascular loops and networks, and microvascular density, a clinically meaningful 0.15 difference in 10-year melanoma-specific survival persisted. CONCLUSIONS: The presence of ezrin immunoreactivity in uveal malignant melanoma is associated with higher mortality and with two independent high-risk characteristics: microvascular density and number of infiltrating macrophages. Further experimental studies on the interrelationship of these three factors may shed light on the progression of uveal melanoma and perhaps that of other cancers.
Antibodies, Monoclonal↗
Human immune response to Puumala virus glycoproteins and nucleocapsid protein expressed in mammalian cells.
Puumala hantavirus (PUUV) glycoproteins G1 and G2 and nucleocapsid protein (N) were expressed in BHK-21 cells by transfection of a plasmid producing a recombinant alphavirus replicon. Coexpression of G1 and G2 from separate constructs seemed to be important for the optimal folding of the glycoproteins, as evaluated by a panel of MAbs detecting conformational epitopes. To evaluate the human antibody response against recombinant G1, G2 and N, several panels of sera were tested by immunofluorescence assay (IFA). Also human sera showed the best reactivity towards G1 and G2 coexpressed from separate transcripts (G1 + G2). Notably, only 2% of the acute sera (total number = 133) contained IgG antibodies against G1 + G2, whereas of old-immunity sera (total number = 100) 87% were G1 + G2 positive. Analysis of a panel of serial patient sera showed that as the immunity matured, IgG antibodies against the recombinant glycoproteins appeared and the titers increased in the course of time, while antibodies against the recombinant N were present already in the acute phase in high titers. The granular fluorescence pattern in PUUV IgG-IFA, associated with the acute phase of immunity, was linked to the presence of antibodies against N, whereas the diffuse fluorescence pattern associated with old-immunity, was linked to the development of antibodies against G1 + G2. The granular fluorescence pattern in PUUV IgG-IFA had a predictive value of 100% for acute PUUV infection. Weak cross-reaction with PUUV glycoproteins was observed in 36% of old-immunity DOBV-specific human sera.
Adolescent↗
Enhanced release of soluble urokinase receptor by endothelial cells in contact with peripheral blood cells.
The urokinase receptor (uPAR) on the cell surface plays an important role in extracellular proteolysis, cell migration and adhesion. Soluble uPAR (suPAR) has been recently discovered in plasma, but its origin is unclear. Our results now demonstrate that both unstimulated blood mononuclear and endothelial cells can release suPAR and that the release is enhanced when either mononuclear cells or thrombocytes are cultured together with endothelial cells. Co-culture without cell-cell contacts fails to enhance suPAR release. We also found suPAR fragments, known to be potent inducers of chemotaxis, in co-culture growth medium samples. Taken together, our results suggest that normal plasma suPAR can be produced by endothelial and mononuclear cells and that suPAR release in cell-cell contacts may have a regulatory role in cell adhesion.
Blood Platelets↗
Soluble urokinase receptor levels correlate with number of circulating tumor cells in acute myeloid leukemia and decrease rapidly during chemotherapy.
The importance of plasminogen activation, mediated by urokinase (uPA) and its receptor (uPAR), is well established in many physiologica and pathological processes, such as in cell migration and tumor-cell invasion. Recently, additional functions have been described for uPA and uPAR, particularly in cell adhesion and chemotaxis. The amounts of uPA and uPAR in various tumor types and in the plasma/serum samples of cancer patients have been shown to correlate with survival prognosis, indicating the relevance of these molecules in malignancy. We previously showed that in acute myeloid leukemia, a high level of plasma soluble uPAR (suPAR) at diagnosis correlates with poor response to chemotherapy. However, in this case, as in other cancers, the origin of suPAR is unknown. Therefore, we have now analyzed uPAR in cells, plasma, and urine of patients with acute leukemia (n = 35) at 0, 5, 14, 28, and 56 days after start of chemotherapy. In response to cytotoxic treatment, suPAR levels decreased rapidly, and the decreasing plasma suPAR (p-suPAR levels correlated highly with decreasing numbers of circulating tumor cells, suggesting that the elevated p-suPAR was produced by circulating tumor cells. Moreover, the p-suPAR level appeared to correlate with the amount of uPAR in tumor cell lysates at diagnosis. Our results also show for the first time that in lysates of circulating tumor cells, studied by immunoprecipitation and immunoblotting, uPAR was partly in fragmented form, whereas only full-length uPAR was found in normal leukocytes. We also detected fragmented suPAR in peripheral blood plasma, in urine, and especially in the plasma compartment of bone-marrow aspirates of acute myeloid leukemia patients, in a pattern differing considerably from that found in healthy individuals. Because proteolytic cleavage of uPAR induces a potent chemotactic response in vitro, it is possible that these fragments may play a role in the pathophysiology of acute leukemia.
Acute Disease↗
Ezrin, a membrane-organizing protein, as a polarization marker of the retinal pigment epithelium in vertebrates.
Immunoreactivity for ezrin, a membrane-organizing phosphoprotein that tethers actin microfilaments to cell membrane proteins, was evaluated as a polarization marker in the intraocular neuroepithelial cells of vertebrates, especially in the retinal pigment epithelium (RPE). Six fetal human eyes representing the 14th-28th gestational weeks, 9 normal adult eyes, 12 eyes with intraocular tumors, and 26 eyes from 15 other vertebrate species were analyzed by immunohistochemistry using the avidin-biotinylated peroxidase complex (ABC) method and monoclonal antibody (mAb) 3C12 to ezrin. The apical cytoplasm and microvilli of the human RPE always reacted with mAb 3C12, but the basal cytoplasm was labeled in reactive RPE only. In autopsy eyes and if fixation was delayed, ezrin immunoreactivity in RPE was more diffuse. Developing RPE became gradually immunoreactive from the 14th week of gestation onward. The microvilli of the baboon, pig, raccoon dog, cow, and rat RPE cells were likewise labeled, and their basal cytoplasm was variably immunoreactive as well, but the microvilli of the avian RPE did not react with the antibody used. In all six mammals mentioned, both layers of the ciliary epithelium and the anterior iris epithelium reacted for ezrin, and the posterior epithelium was weakly labeled in pig, cow, and rat eyes. Normal peripheral and reactive human retina, and normal baboon, pig, raccoon dog, cow, rat, black grouse, and jay eyes, showed immunoreaction for ezrin in Muller cells, usually in their microvilli. Ezrin is widely found in RPE and anterior segment neuroepithelia of the mammalian eye, in which it may segregate membrane proteins to specific membrane surfaces, especially to the apical microvilli of the RPE, which intimately interact with outer segments of photoreceptor cells. The ezrin gene on human chromosome 6q25-26 is consequently a candidate gene for causing retinal degenerations.
Aged↗
Hantavirus infections among mammalogists studied by focus reduction neutralisation test.
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Animals↗
Human herpesvirus-6 associated encephalitis with subsequent infantile spasms and cerebellar astrocytoma.
A 14-month-old girl presented after 3 days of fever, floppiness, and diffuse urticarial exanthem. She developed encephalitis and carditis and 1 week later, intractable seizures. Initial CT and MRI showed no changes in the brain parenchyma. On days 14 and 34 after the onset of symptoms, a human herpesvirus-6 (HHV-6) genome in cerebrospinal fluid was identified by polymerase chain reaction (PCR). Convulsions became more frequent and 11 weeks from the onset, they changed to typical infantile spasms with hypsarrhythmic electroencephalogram. She gradually lost her social contact and ability to walk and sit. Eleven months after the primary infection, a repeated MRI of the brain revealed a cystic tumour of 2 cm in diameter near the vermis. The tumour was surgically removed, and shown to be a pilocytic astrocytoma on histopathological examination. HHV-6 DNA was detected by PCR in new tumour tissue. This is the first reported case of HHV-6 encephalitis associated with carditis, infantile spasms, and a subsequent brain tumour containing the HHV-6 genome.
Astrocytoma↗
Chlamydia trachomatis seropositivity is associated both with stillbirth and preterm delivery.
The cause of stillbirth and preterm delivery is often unknown. We studied the prevalence of Chlamydia trachomatis antibodies in mothers with stillbirth and preterm labor. Serum specimens from 72 mothers with stillbirth after the 21st gestational week, and from 48 mothers with preterm delivery between gestational weeks 23 and 29, both from the greater Helsinki area, and cord blood from 96 consecutive liveborn deliveries at the Department of Obstetrics and Gynecology, the University of Helsinki, were studied for antibodies to C. trachomatis immunotypes CJHI, GFK and BED by microimmunofluorescence test. The prevalence of C. trachomatis antibodies was highest, 33.3%, in mothers with stillbirth, 18.8% in mothers with preterm delivery, and 10.4% in cord blood. The IgM seropositivity rate was high among mothers with preterm delivery (8.3%). We conclude that C. trachomatis IgG antibodies are frequently detected in sera from mothers with stillbirth, suggesting past infection, while mothers with preterm delivery often have serum IgM antibodies, suggesting of acute infection.
Acute Disease↗
Renal function and blood pressure five years after puumala virus-induced nephropathy.
BACKGROUND: Nephropathia epidemica (NE) is a mild form of hemorrhagic fever with renal syndrome caused by Puumala hantavirus. Its long-term prognosis is considered favorable. Some reports suggest, however, that a previous hantavirus infection increases the risk of hypertension. METHODS: We studied 46 previously healthy subjects (26 males and 20 females, mean age of 44 years) who had serologically confirmed NE three to seven years previously, and 38 healthy, seronegative controls (22 males and 16 females, mean age of 44 years). Ambulatory blood pressure (ABP) was monitored. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined by 51CrEDTA and 131I-hippurate clearances, respectively. The filtration fraction (FF) was calculated. Quantitative 24-hour urinary protein excretion (UprotE) and timed overnight urinary excretion of alpha1-microglobulin were measured. RESULTS: The NE patients had a higher mean ambulatory systolic BP than the controls (123 +/- 13 vs. 117 +/- 9 mm Hg, P = 0. 008). GFR and FF were increased in patients compared with controls (GFR, 120 +/- 20 vs. 109 +/- 14 mL/min/1.73 m2, P = 0.006; FF, 19 +/- 3 vs. 18 +/- 3%, P = 0.030), but ERPF did not differ between the groups. The patients also had higher UPE than the controls (median 0. 18 g/day, range 0.12 to 0.38 vs. median 0.14 g/day, range 0.09 to 0. 24, P < 0.001, respectively). The overnight urinary excretion rate of alpha1-microglobulin exceeded 7 microg/min in nine patients. CONCLUSION: Three to seven years after NE, the patients had higher GFR and FF, more proteinuria, and higher ambulatory systolic BP compared with the healthy controls. NE may thus cause mild renal lesions and alterations in BP in some patients.
Acute Kidney Injury↗
Molecular evolution of puumala hantavirus in Fennoscandia: phylogenetic analysis of strains from two recolonization routes, Karelia and Denmark.
Like other members of the genus HANTAVIRUS: in the family BUNYAVIRIDAE:, Puumala virus (PUUV) is thought to be co-evolving with its natural host, the bank vole Clethrionomys glareolus. To gain insight into the evolutionary history of PUUV in northern Europe during the last post-glacial period, we have studied wild-type PUUV strains originating from areas along two postulated immigration routes of bank voles to Fennoscandia. Full-length sequences of the S RNA segment and partial sequences (nt 2168-2569) of the M segment were recovered by RT-PCR directly from bank vole tissues collected at three locations in Russian Karelia and one location in Denmark. Phylogenetic analysis showed that strains from Karelia and Finland belong to the same genetic lineage, supporting the hypothesis that PUUV spread to present Finland via a Karelian land-bridge. The Danish PUUV strains showed no particularly close relatedness to any of the known PUUV strains and formed a distinct phylogenetic lineage on trees calculated for both S and M segment sequences. Although no direct link between the Danish PUUV strains and those of the southern Scandinavian lineage was found, within the S segment of Danish PUUV strains, two regions with higher similarity to either northern Scandinavian or - to a less extent - southern Scandinavian genetic lineages were revealed, suggesting evolutionary connections of their precursors.
Amino Acid Sequence↗
Genetic analysis of wild-type Dobrava hantavirus in Slovenia: co-existence of two distinct genetic lineages within the same natural focus.
Genetic analysis was performed of wild-type (wt) Dobrava hantavirus (DOB) strains from Slovenia, the country where the virus was first discovered and where it was found to cause haemorrhagic fever with renal syndrome (HFRS), with a fatality rate of 12%. Two hundred and sixty mice of the genus APODEMUS:, trapped in five natural foci of DOB-associated HFRS during 1990-1996, were screened for the presence of anti-hantavirus antibodies and 49 APODEMUS: flavicollis and four APODEMUS: agrarius were found to be positive. RT-PCR was used to recover partial sequences of the wt-DOB medium (M) and small (S) genome segments from nine A. flavicollis and one A. agrarius. Sequence comparison and phylogenetic analysis of the Slovenian wt-DOB strains revealed close relatedness of all A. flavicollis-derived virus sequences (nucleotide diversity up to 6% for the M segment and 5% for the S segment) and the geographical clustering of genetic variants. In contrast, the strain harboured by A. agrarius showed a high level of genetic diversity from other Slovenian DOB strains (14%) and clustered together on phylogenetic trees with other DOB strains harboured by A. agrarius from Russia, Estonia and Slovakia. These findings suggest that the DOB variants carried by the two species of APODEMUS: in Europerepresent two distinct genetic lineages.
Animals↗
Detection of human herpesvirus 6 and varicella-zoster virus in tear fluid of patients with Bell's palsy by PCR.
Human herpesvirus 6 DNA was detected by PCR in the tear fluid of 7 (35%) of 20 patients with Bell's palsy and of 1 (5%) of 20 healthy controls. Varicella-zoster virus was detected by PCR in the tear fluid of 2 of 20 Bell's palsy patients but in none of the tear fluids from 20 healthy controls. These findings suggest an association between human herpesviruses and Bell's palsy.
Adult↗
In situ hybridization detection of human herpesvirus 6 in brain tissue from fatal encephalitis.
A 23-month-old girl died after 2 days' illness with rash, fever, and convulsions. Neuropathologic findings were consistent with viral hemorrhagic encephalitis in pontine tegmentum and medial thalamic areas. Human herpesvirus 6 (HHV-6) DNA was detected in pontine nuclei by in situ hybridization. In addition, polymerase chain reaction for HHV-6 of serum and paraffin-embedded pontine tissue was positive, and serology indicated an acute primary infection. This is the first case showing HHV-6 DNA in the brain cells of an immunocompetent patient with acute encephalitis.
Brain↗
Antigenic properties and diagnostic potential of recombinant dobrava virus nucleocapsid protein.
Dobrava hantavirus (DOBV) causes severe hemorrhagic fever with renal syndrome in the Balkan region and has been detected recently also in Russia, Estonia, and Germany. DOBV nucleocapsid protein (N) was produced in insect cells, using the baculovirus expression system (bac-DOBV-N), and in E. coli as a truncated (aa 1-165) glutathione-S transferase fusion protein (DOBV-dN-GST). The antigenic properties of bac-DOBV-N were found identical to native DOBV-N when examined by a panel of hantavirus-specific monoclonal antibodies. Enzyme immunoassays for detection of IgM and IgG antibodies were set up using DOBV recombinant N proteins and compared with those based on recombinant Hantaan and Puumala virus N, using panels of sera collected from DOBV, Hantaan and Puumala virus-infected patients. Full-length N protein (bac-DOBV-N) was found to be a more sensitive antigen than DOBV-dN-GST. The sensitivity values for sera from DOBV-infected patients were 100% for bac-DOBV-N and 86% for DOBV-dN-GST by IgM assays, and 98% for bac-DOBV-N and 88% for DOBV-dN-GST by IgG assays. The specificity values were 100% for bac-DOBV-N and 99% for DOBV-dN-GST by IgM assays, and 100% for both antigens by IgG assays.
Antigens, Viral↗
[Nephropathia epidemica and other hanta virus infections: how rodents' viruses cause disease in human?].
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Animals↗